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Purpose The purpose of this article was to provide a review for hearing care providers of the need for improving the auditory signal for older adults who are often faced with hearing challenges in medical settings. Personal devices worn at the ear level may not reduce communication challenges that result from noise, reverberation, and distance. The use of a remote microphone may greatly enhance the audibility of the health care provider's voice and reduce the stress caused by miscommunication. Suggestions for optimal use of remote microphone technology in medical settings are provided in 3 settings: office appointment, hospital stays, and living with caregivers/nurses. Conclusions Use of remote microphone technology in conjunction with personal ear-level technology may significantly facilitate communication in the health care setting. In addition to providing a higher quality signal when worn by a speaker, the microphone may serve as a reminder to the health care provider to speak more slowly and clearly, as well as to ask for confirmation that the correct information was received.

Aims Left atrial appendage (LAA) occlusion with first generation Ultraseal device (Cardia, Eagan, Minnesota) has been shown to be a feasible therapeutic option in patients with non-valvular atrial fibrillation (NVAF). However, there is a paucity of data regarding the novel Ultraseal device. To assess feasibility and safety of second generation LAA closure Ultraseal device in patients with NVAF. Methods and results All patients with NVAF undergoing second generation Ultraseal device implantation between February 2018 and September 2020 were included in a multicentre international registry. Periprocedural and post-discharge events were collected up to 6-months follow-up. Primary efficacy endpoints of interest were device success and technical success; primary safety endpoint was in-hospital major adverse events occurrence. A total of 52 patients were included: mean age 75 ± 8, 69.2% male, mean HAS-BLED 3 ± 1. The device was successfully implanted in all patients. Technical success was achieved in 51 patients (98.0%). In-hospital major adverse event occurred in three patients (5.8%). The incidence of 6-months all-cause death and major bleeding was 11.6% and 2.1%, respectively. No strokes, transient ischaemic attacks, systemic embolisms or device embolization were reported. Conclusions Second generation Ultraseal Device implantation was associated with high procedural success rate and a low incidence of peri-procedural complications. Larger studies with longer follow-up are warranted to evaluate the safety and the efficacy of this device, especially at medium and long term follow-up.

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p < 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived angiotensinogen (Agt) and the generation of intrarenal angiotensin (Ang) II and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin knockout (KO) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2. Without podocyte injury, renal Agt staining was markedly diminished and urinary Agt increased in KO mice. However, renal Ang II was similar between KO and control mice on average: 117 (95% CI 101–134) vs. 101 (68–133) fmol/g tissue. We next tested the effect of megalin KO on intrarenal Ang II generation with podocyte injury. Control NEP25 mice showed markedly increased renal Agt staining and renal Ang II levels: 450 (336–565) fmol/g tissue. Megalin KO/NEP25 mice showed markedly diminished Agt reabsorption and attenuated renal Ang II: 199 (156–242) fmol/g tissue (p < 0.001). Compared with control NEP25 mice, megalin KO/NEP25 mice excreted 5-fold more sodium in the urine. Western blot analysis showed that megalin KO decreased NHE3 and the cleaved α and γ forms of ENaC. These data indicate that Agt reabsorbed by proximal tubules via megalin in nephrotic syndrome is converted to Ang II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC. SUMMARY: This study shows that in nephrotic syndrome, plasma angiotensinogen leaked into the renal tubular lumen is reabsorbed by proximal tubules via megalin and converted to angiotensin II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC.

7-Lithio-3- tert -butylpyrazolo[5,1- c ][1,2,4]triazines have been generated for the first time using one-pot nucleophilic addition and metal-halogen exchange reactions in 7-bromopyrazolo[5,1- c ][1,2,4]triazines. It was found that the stability of 7-lithio species depends highly on the substitution pattern at the C(4) ring position. The rate of the pyrazole ring opening reaction roughly followed the order of the electronegativity of substituents: rapid cycle cleavage took place already at −97 °C for C(4) = O, CH–Ar, CH–C≡CPh, while CH–Alk and CH 2 substituted derivatives were stable in these conditions (Ar = Ph, 4-tolyl; Alk = t -Bu, n -Bu, n -Pr). Quantum chemical modeling showed that the ring opening is accompanied with simultaneous shift of the Li atom towards N(6). Calculated free activation energies are in range from 12.7 to 15.0 kcal/mol. Electrophile trapping of fairly stable 4-alkyl-1,7-metalated derivatives at −97 °C using H 2 O, DMF or PhCHO allowed the selective side-chain functionalization. Tautomeric exo- and endocyclic double bond equilibrium in the isolated 4-oxo and 4-aryl substituted ring opening products is also discussed on the basis of IR, 1 H, 13 C NMR, high resolution mass spectra and X-ray powder diffraction analysis.

The origin of the interstellar object 1I/'Oumuamua, has defied explanation. In a companion paper (Jackson & Desch, 2021), we show that a body of N2 ice with axes 45 m x 44 m x 7.5 m at the time of observation would be consistent with its albedo, non-gravitational acceleration, and lack of observed CO or CO2 or dust. Here we demonstrate that impacts on the surfaces of Pluto-like Kuiper belt objects (KBOs) would have generated and ejected ~10^14 collisional fragments--roughly half of them H2O ice fragments and half of them N2 ice fragments--due to the dynamical instability that depleted the primordial Kuiper belt. We show consistency between these numbers and the frequency with which we would observe interstellar objects like 1I/'Oumuamua, and more comet-like objects like 2I/Borisov, if other stellar systems eject such objects with efficiency like that of the Sun; we infer that differentiated KBOs and dynamical instabilities that eject impact-generated fragments may be near-universal among extrasolar systems. Galactic cosmic rays would erode such fragments over 4.5 Gyr, so that fragments are a small fraction (~0.1%) of long-period Oort comets, but C/2016 R2 may be an example. We estimate 'Oumuamua was ejected about 0.4-0.5 Gyr ago, from a young (~10^8 yr) stellar system, which we speculate was in the Perseus arm. Objects like 'Oumuamua may directly probe the surface compositions of a hitherto-unobserved type of exoplanet: "exo-plutos". 'Oumuamua may be the first sample of an exoplanet brought to us., 29 pages, 1 figure. Companion to Jackson & Desch (2021), "1I/'Oumuamua as an N2 ice fragment of an exo-pluto surface. I. Size and compositional constraints"

The conversion of ≡Fe(III) to ≡Fe(II) in the heterogeneous Fenton is low efficient to enhance catalytic activity. Biogenic schwertmannite (Sch), as an iron-based catalyst, is usually formed via Fe(II) oxidation mediated by Acidithiobacillus ferrooxidans (A. ferrooxidans), and contains low organic carbon mainly originated from exopolymeric substances. Owing to the magnetic inter-attraction between A. ferrooxidans and Fe3O4, the introduction of strong magnetic Fe3O4 during synthesis process of biogenic Sch can modify more organic carbon in Sch-based catalyst. Surprisingly, Fe3O4-loaded Sch with organic carbon (Fe3O4/Sch/C) exhibits much higher activity for fluoroquinolone antibiotics degradation than Sch, Fe3O4, and Fe3O4-loaded Sch without organic carbon, which is mainly ascribed to more electrons provided by organic carbons for promoting ≡Fe(II) generation in heterogeneous Fenton. This finding not only provides an ecofriendly, cost-effective, and efficient catalyst, but also gives a new sights into the potential application of iron oxyhydroxysulfate with green carbon-source for contaminants removal.

We describe a novel approach to functionalization of graphene oxide (GO) which allows for a facile generation of paramagnetic centers from two diamagnetic components. Coordination attachment of [Ni(cyclam)] 2+ or [Ni(tet b )] 2+ tetraazamacrocyclic cations to carboxylic groups of GO takes place under basic conditions in aqueous-based reaction medium. The procedure is very straightforward and does not require high temperatures or other harsh conditions. Changing the coordination geometry of Ni(II) from square-planar tetracoordinated to pseudooctahedral hexacoordinated brings about the conversion from low-spin to high-spin state of the metal centers. Even though the content of tetraazamacrocyclic complexes in functionalized GO samples was found to be relatively low (nickel content of ca. 1 wt%, as determined by thermogravimetric analysis, elemental analysis and energy dispersive X-ray spectroscopy), room temperature magnetic susceptibility measurements easily detected the appearance of paramagnetic properties in GO + [Ni(cyclam)] and GO + [Ni(tet b )] nanohybrids, with effective magnetic moments of 1.95 BM and 2.2 BM for, respectively. According to density functional theory calculations, the main spin density is localized at the macrocyclic complexes, without considerable extension to graphene sheet, which suggests insignificant ferromagnetic coupling in the nanohybrids, in agreement with the results of magnetic susceptibility measurements. The coordination attachment of Ni(II) tetraazamacrocycles to GO results in considerable changes in Fourier-transform infrared and X-ray photoelectron spectra, as well as in GO morphology, as observed by scanning and transmission electron microscopy, atomic force and scanning tunneling microscopy.

The renal tissue renin-angiotensin system is activated in chronic kidney diseases. We previously demonstrated that intrarenal ANG II is synthesized primarily from liver-derived angiotensinogen filtered through the glomerulus and that podocyte injury increases the passage of angiotensinogen into the tubular lumen and generation of ANG II. In the present study, we tested the effect of cessation of glomerular filtration by ureteral obstruction on renal ANG II generation in kidneys with podocyte injury under two experimental conditions. Ureteral obstruction is known to activate the renin-angiotensin system in nonproteinuric kidneys. Transgenic mice expressing hCD25 in podocyte (NEP25) were injected with 1.25 or 10 ng/g body wt of LMB2, a hCD25-targeted immunotoxin, subjected to unilateral ureteral ligation on the following day, and euthanized 7 and 4 days later, respectively. In both experiments, compared with the kidney in untreated wild-type mice, renal angiotensinogen protein, as assessed by immunostaining and Western blot analysis, was increased in the contralateral unobstructed kidney. However, it was markedly decreased in the obstructed kidney. Whereas intrarenal ANG II content was increased in the contralateral kidney compared with the untreated kidney (248 ± 83 vs. 106 ± 21 and 298 ± 185 vs. 64.8 ± 20 fmol/g kidney, respectively), this increase was suppressed in the obstructed kidney (161 ± 75 and 113 ± 34 fmol/g kidney, respectively), a pattern opposite to what we expected in obstructed kidneys without podocyte injury. Thus, our study indicates that the major source of increased renal ANG II in podocyte injury is filtered angiotensinogen.